1. Introduction
Giardiasis continues to be a significant parasitic disease in the world caused by the species of
2. Overview and general aspects of giardiasis
3. Epidemiology
Distributed worldwide,
In developed countries, giardiasis is associated with social and climatic factors and is referred as a re-emerging infectious agent. Some epidemiological studies have shown that its prevalence varies between the population studied and the location, from 2 to 5% on industrialized countries to 20–30% in developing countries [1, 5, 11], and these changes in prevalence are associated, among others, with the hygiene infrastructure and the impact of the weather conditions, reason why environmental control efforts are necessary, which requires an integrated and systematic approach to decrease and mitigate the influence on the disease epidemiology; for this reason, it is linked to educational programs and other interventional measures [2, 6, 12].
Although in Latin America, a restricted quantity of population-based studies has been performed, in Cuba, according to the last national intestinal parasites survey (n = 5850), the prevalence of
This parasitosis is highly infectious where
4. Life cycle
The trophozoite, which is 9–21 μm long, 5–15 μm wide, and 2–4 μm thick, lives in the small intestine and is responsible for many manifestations of the disease. The cytoskeleton composed of unique families of structural proteins and carbohydrates involves two nuclei, a ventral sucking adhesive disk by which it may adhere to intestinal epithelial cells, a median body, and four pairs of flagella that behave differently during motility. The dorsal surface is pear shaped and bilaterally symmetrical, with the two highly characteristic nuclei best visualized after staining. The newly emerged trophozoites infect the duodenum and jejunum where there is a favorable alkaline pH; they attach intimately to the intestinal epithelium by their ventral disk and begin to multiply by binary fission. Detection of soluble cyst wall proteins in the feces forms the basis of many stool antigen assays [1, 8, 16, 17].
When the trophozoite senses a change in the environment as the cell is transported further down in the small intestine, it starts the encystation; in the earliest moment of this process, some specific vesicles are designed that allow its development and maturation, probably as a result of cholesterol starvation. At the same time with several proteins implicated in metabolic pathways, after that, several proteins also change their expression by important gene expression changes.
Giardiasis as a multifactorial disease involves in its pathobiology complex interactions between host and parasite, differences in nutritional status, immune status, co-infections, and intestinal normal flora that could contribute to the differences in disease outcome observed among individuals from developing against developed countries. The roles of the host’s intestinal normal flora and co-infections during
Some morphologically identical but genetically distinct
The two assemblages (A and B) are composed of genetically distinguishable isolates, which may vary in infectivity, antigenicity, and virulence. In addition, human hosts vary in susceptibility to infection and disease and in the response to tolerance to infection. In this way,
5. Clinical aspects
The clinical manifestations, course, and duration of
The first signs of infection appear after 6–15 days. Most symptomatic infections resolve spontaneously; however, sometimes, hospitalization is required when infections have long-term consequences and do not respond to the normal treatment. Chronic
In some cases, if acute symptoms are not treated on time, they can develop into a chronic stage, which can affect all age groups but children are at higher risk, in whom
A typical scenario is a mildly to moderately ill person who grumbles of a raised number of urgent loose stools, with flatus, cramping, anorexia, and weight loss. There may even be periods when the person feels better only to relapse and then become noticeably worse. Finally, after some days to several weeks, the person will seek medical help. Similar to other causes of infectious diarrheas, symptoms can carry on after successful treatment and evolve into irritable bowel syndrome and chronic fatigue, even 6 years after the infection. Infrequently,
6. Diagnostics
The diagnosis of giardiasis is based on the detection of cysts, trophozoites, or parasite-specific antigens in fecal microscopic examination, complemented with microscopic examination of duodenal fluids or in other biological samples. Polymerase chain reaction has been largely experimental, but it is being increasingly used in field and laboratory settings; considering that excretion of cysts may be variable or in low concentrations (50–80% sensitive), two or three checkups may be necessary, leading to a late diagnosis (>2 weeks) [3]. Stool antigen tests are standard in most laboratories and are highly sensitive (>90%), specific (~100%), and relatively inexpensive and do not require a trained microscopist [2, 9, 13, 18].
The observation of small intestine biopsy specimens or intestinal contents for trophozoites was the previous “gold standard” for diagnosis, but now, it is uncommonly needed to establish or to confirm the diagnosis. A number of morphological characteristics of the trophozoite can be used for the initial diagnostic, but it is not possible to identify which specific species by light microscopy, the reason why another type of test could be used in the medical approach. Electron microscopy might be useful for the identification of some
The use of immunological methods offers an important alternative for the diagnosis. The use of fluorescence microscopy and the direct fluorescence antibody test, which recognizes surface epitopes on cysts, has been reported to achieve relatively high specificity (99.8–100%) and sensitivity (93–100%) for the detection. The detection of
In some cases, the laboratory findings are nonspecific, and in low-intensity infections, testing methods can be false negative for which it is required to repeat the test. On the other hand, the white blood cell count and liver function test results used to be normal. The electrolyte disturbances could be present if diarrhea and vomiting are severe. White blood cells, lactoferrin, blood, and mucus are not found in stools. Immunoglobulin levels are usually normal but usually low or absent in susceptible hypogammaglobulinemic individuals [2, 3].
7. Treatment
During the last 60 years of the past century, the arsenal of antigiardial drugs has been increasing, and they still are in use. Before the introduction of quinacrine, these infections were treated with mercury, carbon tetrachloride, arsenicals, and bismuth; at present, an important number of agents have shown to be efficacious against
The 5-nitroimidazole (5-NI) derivatives remain the most frequently prescribed drugs, as well as metronidazole, tinidazole, and secnidazole. In spite of their efficacy, the treatment with these drugs is associated with several adverse effects, which are not always tolerable such as headache, metallic or bitter taste in mouth, nausea, vomiting, diarrhea, dizziness, general body discomfort, loss of appetite, etc. Whereas medical opposition may limit the use of some of them in singular cases, as in pediatrics, where their dose requirements make difficult the administration of tablet formulations to children. Finally, in the follow-up of some patients after treatment to evaluate the response to antigiardial drugs, a therapeutic failure is identified [4, 7, 21, 22].
Nitazoxanide is a new very broad spectrum 5-nitrothiazolyl derivative with a potentially useful activity against a range of biological agents. The effect of nitazoxanide in
Some patients, who are being treated with the standard treatment that cures other patients, can continue with symptoms. In these cases, there are possibilities of different situations, including drug resistance, cure followed by reinfection, and also noncompliance and post
When there is a resistant
8. Control and prevention
The interest in
This pathogen has been highlighted for the importance in terms of patient well-being and its effects on quality of life for being a continuing cause of the patient’s discomfort and pain. Unfortunately, due to a lack of political will, funding, interest from the scientific community, or the combination of all of these factors, giardiasis is not a health priority; that is why, it is important to take in mind that this infection is prevented by a scrupulous personal hygiene, proper disposal of sewage, removal or killing of cysts from water supplies, and preventing contamination of food and water [2, 20].
Actually, the global burden of chronic giardiasis is not known, and the difficulties in diagnostic tools, the lack of definition, and difficulties to quantify the impact of an infection that causes an acute or chronic one, principally symptomatic illness, contribute to the necessity to realize studies that estimate the problems in terms of cost, day lost for disability, and quality of life [9, 18].
Despite that, important contributions have been made regarding the spectrum of illness attributable to giardiasis. It is illustrated in the protective effect of
References
- 1.
Escobedo AA, Cimerman S. Giardiasis: A pharmacotherapy review. Expert Opinion on Pharmacotherapy. 2007; 8 (12):1885-1902 - 2.
Robertson LJ, Hanevik K, Escobedo AA, Morch K, Langeland N. Giardiasis—Why do the symptoms sometimes never stop? Trends in Parasitology. 2010; 26 (2):75-82 - 3.
Almirall P, Alfonso M, Ávila I, Salazar Y, Escobedo AA, Núñez FA, et al. Variaciones en las manifestaciones clínicas de la giardiosis en pacientes pediátricos hospitalizados, según grupos de edades. Revista Chilena de Infectología. 2013; 30 (5):502-506 - 4.
Pasupuleti V, Escobedo AA, Deshpande A, Thota P, Roman Y, Hernandez AV. Efficacy of 5-nitroimidazoles for the treatment of giardiasis: A systematic review of randomized controlled trials. PLoS Neglected Tropical Diseases. 2014; 8 (3):e2733 - 5.
Escobedo AA, Almirall P, Alfonso M, Cimerman S, Chacin-Bonilla L. Sexual transmission of giardiasis: A neglected route of spread? Acta Tropica. 2014; 132 :106-111 - 6.
Ryan U, Caccio SM. Zoonotic potential of Giardia . International Journal for Parasitology. 2013;43 (12-13):943-956 - 7.
Escobedo AA, Arencibia R, Vega RL, Rodriguez-Morales AJ, Almirall P, Alfonso M. A bibliometric study of international scientific productivity in giardiasis covering the period 1971-2010. Journal of Infection in Developing Countries. 2015; 9 (1):76-86 - 8.
Escobedo AA, Lalle M, Hrastnik NI, Rodriguez-Morales AJ, Castro-Sanchez E, Cimerman S, et al. Combination therapy in the management of giardiasis: What laboratory and clinical studies tell us, so far. Acta Tropica. 2016; 162 :196-205 - 9.
Escobedo AA, Hanevik K, Almirall P, Cimerman S, Alfonso M. Management of chronic Giardia infection. Expert Review of Anti-infective Therapy. 2014;12 (9):1143-1157 - 10.
Halliez MC, Buret AG. Extra-intestinal and long term consequences of Giardia duodenalis infections. World Journal of Gastroenterology. 2013;19 (47):8974-8985 - 11.
Rodriguez-Morales AJ, Granados-Alvarez S, Escudero-Quintero H, Vera-Polania F, Mondragon-Cardona A, Diaz-Quijano FA, et al. Estimating and mapping the incidence of giardiasis in Colombia, 2009-2013. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases. 2016; 49 :204-209 - 12.
Escobedo AA, Almirall P, Rumbaut R, Rodriguez-Morales AJ. Potential impact of macroclimatic variability on the epidemiology of giardiasis in three provinces of Cuba, 2010-2012. Journal of Infection and Public Health. 2015; 8 (1):80-89 - 13.
Almanza C, Escobedo AA, Rodriguez-Morales AJ. Giardia infection in foreign visitors to Cuba. Travel Medicine and Infectious Disease. 2015;13 (6):505-506 - 14.
Thompson RC, Monis PT. Variation in Giardia : Implications for taxonomy and epidemiology. Advances in Parasitology. 2004;58 :69-137 - 15.
Einarsson E, Ma'ayeh S, Svard SG. An up-date on Giardia and giardiasis. Current Opinion in Microbiology. 2016;34 :47-52 - 16.
Birkeland SR, Preheim SP, Davids BJ, Cipriano MJ, Palm D, Reiner DS, et al. Transcriptome analyses of the Giardia lamblia life cycle. Molecular and Biochemical Parasitology. 2010;174 (1):62-65 - 17.
Carranza PG, Lujan HD. New insights regarding the biology of Giardia lamblia. Microbes and Infection. 2010;12 (1):71-80 - 18.
Koehler AV, Jex AR, Haydon SR, Stevens MA, Gasser RB. Giardia /giardiasis—A perspective on diagnostic and analytical tools. Biotechnology Advances. 2014;32 (2):280-289 - 19.
Duran C, Hidalgo G, Aguilera W, Rodriguez-Morales AJ, Albano C, Cortez J, et al. Giardia lamblia infection is associated with lower body mass index values. Journal of infection in developing countries. 2010;4 (6):417-418 - 20.
Escobedo AA, Almirall P, Cimerman S, Rodriguez-Morales AJ. Sequelae of giardiasis: An emerging public health concern. International Journal of Infectious Diseases: IJID: Official Publication of the International Society for Infectious Diseases. 2016; 49 :202-203 - 21.
Escobedo AA, Ballesteros J, Gonzalez-Fraile E, Almirall P. A meta-analysis of the efficacy of albendazole compared with tinidazole as treatments for Giardia infections in children. Acta Tropica. 2016;153 :120-127 - 22.
Rodriguez-Morales AJ, Martinez-Pulgarin DF, Munoz-Urbano M, Gomez-Suta D, Sanchez-Duque JA, Machado-Alba JE. Bibliometric assessment of the global scientific production of nitazoxanide. Cureus. 2017; 9 (5):e1204